The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo

• Published in: Neuroscience Vol. 183; pp. 251 - 264
• Main Authors: Lecanu, L, Hashim, A.I, McCourty, A, Giscos-Douriez, I, Dinca, I, Yao, W, Vicini, S, Szabo, G, Erdélyi, F, Greeson, J, Papadopoulos, V
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 02.06.2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain - cytology; Brain - drug effects; Bromodeoxyuridine - metabolism; Carrier Proteins - metabolism; Cell Differentiation - drug effects; Cell Line; Fundamental and applied biological sciences. Psychology; GAP43; Gene Expression Regulation - drug effects; Humans; Male; Mice; Microtubule-Associated Proteins - metabolism; Nerve Tissue Proteins - metabolism; Neurites - drug effects; neurogenesis; Neurogenesis - drug effects; Neurology; Neurons - cytology; Neurons - drug effects; Neuropeptides - metabolism; neurosteroids; Protein Binding - drug effects; Radioimmunoassay - methods; Rats; Rats, Long-Evans; Receptors, GABA-A - metabolism; Solanaceous Alkaloids - pharmacology; solasodine; Steroids - pharmacology; subventricular zone; Teratocarcinoma - pathology; Time Factors; TSPO; Vertebrates: nervous system and sense organs; doublecortin; 18-kDa translocator protein; solasodine; neurosteroids; DMSO; gamma-aminobutyric acid type A receptor; phosphate buffer; paraformaldehyde 4; PFA; CNPase; RIPA; GFP; dimethyl sulfoxide; MAP2; GABA-A; glutamic acid decarboxylase 65-kDa; neurogenesis; ChAT; TSPO; Alzheimer's disease; PBS; subventricular zone; polyvinylidene difluoride; AD; phosphate buffer saline; green fluorescent protein; PVDF; GAD65; GFAP; growth associated protein-43-kDa; GAP43; 2′,3′-cyclic nucleotide 3′ phosphodiesterase; PB; choline acetyltransferase; DCX; microtubule associated protein-2; radio-immunoprecipitation assay; glial fibrillary acidic protein; Neurosteroid; In vitro; Neurogenesis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.03.042

Abstract In this study, we explored the capacity of the naturally occurring compound solasodine to promote neurogenesis in vitro and in vivo . Mouse embryonic teratocarcinoma P19 cells exposed to solasodine for 2 days followed by a 5-day washout differentiated into cholinergic neurons that expressed specific neuronal markers and displayed important axonal formation that continued growing even 30 days after treatment. In vivo , a 2-week infusion of solasodine into the left ventricle of the rat brain followed by a 3-week washout resulted in a significant increase in bromodeoxyuridine uptake by cells of the ependymal layer, subventricular zone, and cortex that co-localized with doublecortin immunostaining, demonstrating the proliferative and differentiating properties of solasodine on neuronal progenitors. In addition, these data demonstrate that under our experimental conditions adult ependymal cells retrieved their proliferative and differentiating abilities. The GAP-43/HuD pathway was activated both in vitro and in vivo , suggesting a role in the differentiating process triggered by solasodine. Solasodine treatment in rats resulted in a dramatic increase in expression of the cholesterol- and drug-binding translocator protein in ependymal cells, suggesting a possible role played by neurosteroid production in solasodine-induced neurogenesis. In GAD65-GFP mice that express the green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa promoter, solasodine treatment increased the number of GABAergic progenitors and neuroblasts generated in the subventricular zone and present in the olfactory migratory tract. Taken together, these results suggest that solasodine offers an interesting approach to stimulate in situ neurogenesis from resident neuronal progenitors as part of neuron replacement therapy.